Increased monocyte turnover is associated with interstitial macrophage accumulation and pulmonary tissue damage in
Yanhui Cai1, Chie Sugimoto1, David Xianhong Liu1
1Divisions of *Immunology, Comparative Pathology, and Microbiology, Tulane National Primate Research Center, Covington, Louisiana, USA; Departments of Microbiology and Immunology, School of Medicine, and Tropical Medicine, School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana, USA; and Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, Virginia, USA.
Abstract:
We recently reported that increasing blood monocyte turnover that was associated with tissue macrophage death better predicts terminal disease progression in adult SIV-infected macaques than does declining CD4(+) T cell levels. To understand better mechanisms of pathogenesis, this study relates severity of lung-tissue damage to the ratio, distribution, and inflammatory responses of lung macrophage subsets during SIV infection in rhesus macaques exhibiting varying rates of monocyte turnover. In vivo BrdU incorporation was used to evaluate kinetics of monocyte/tissue macrophage turnover. Tissue damage was scored microscopically from H&E-stained lung-tissue sections, and cytokine expression was examined via immunohistochemistry and confocal microscopy. Increased monocyte turnover in SIV-infected rhesus macaques significantly correlated with severity of lung-tissue damage, as exhibited by perivasculitis, vasculitis, interstitial pneumonia, alveolar histiocytosis, foamy macrophages, multinucleated giant cells, fibrin, and edema in the alveoli. In addition, the higher monocyte turnover correlated with declining AI ratio, increased accumulation of IM in the perivascular region of the lung, and higher expression of IL-6 in the IM of the lung tissue exposed to a LPS, calcium ionophore, and tumor promoter combination stimulation ex vivo. Accumulation of IM associated with increasing monocyte turnover during SIV infection appears to contribute to chronic pulmonary inflammation and tissue damage during disease progression to AIDS.
Insights
Increased blood monocyte turnover in SIV-infected macaques correlates with severe lung damage and chronic inflammation. This finding highlights monocyte dynamics as a key factor in AIDS pathogenesis and progression.
Area of Science:
- Immunology
- Pathogenesis
- Primate Models
Background:
- Declining CD4(+) T cell levels are a traditional marker for AIDS progression.
- Increasing blood monocyte turnover, linked to tissue macrophage death, better predicts disease progression in SIV-infected macaques.
Purpose of the Study:
- To investigate the relationship between lung tissue damage severity and macrophage subset dynamics during SIV infection.
- To understand the role of monocyte turnover in pulmonary pathogenesis in SIV-infected rhesus macaques.
Main Methods:
- In vivo BrdU incorporation to assess monocyte/tissue macrophage turnover kinetics.
- Microscopic scoring of H&E-stained lung sections for tissue damage.
- Immunohistochemistry and confocal microscopy for cytokine expression analysis.
Main Results:
- Higher monocyte turnover significantly correlated with increased lung tissue damage, including perivasculitis, vasculitis, and interstitial pneumonia.
- Increased monocyte turnover was associated with a declining AI ratio and accumulation of interstitial macrophages (IM) in lung perivascular regions.
- Elevated IL-6 expression in IM was observed in macaques with higher monocyte turnover.
Conclusions:
- Increasing monocyte turnover is a significant predictor of lung tissue damage severity in SIV-infected macaques.
- Accumulation of interstitial macrophages, driven by monocyte turnover, contributes to chronic pulmonary inflammation and tissue damage during SIV infection.
- Monocyte turnover dynamics offer insights into AIDS pathogenesis and potential therapeutic targets.
